Insulin and Endothelial Function: Physiological Environment Defines Effect on Atherosclerotic Risk

摘要

A number of population studies have suggested that hyperinsulinaemia is an independent risk factor for thendevelopment of cardiovascular atherosclerosis. Furthermore, there is an emerging body of evidence supporting a role forninsulin as both a vasoregulatory and glucoregulatory peptide. Principal amongst insulin’s putative vascular effects is tonstimulate release of the anti-atherosclerotic signalling molecule nitric oxide (NO) from endothelial cells. Moreover, therenis data demonstrating that in parallel to insulin mediated glucose uptake, stimulation of NO release by insulin is blunted inninsulin resistant conditions.nA number of in-vitro studies have begun to dissect and define the pathway by which insulin stimulates release of NO fromnendothelial cells and complimentary studies in gene-modified murine models of abnormal insulin signalling and/ornhyperinsulinaemia have begun to elucidate the role of hyperinsulinaemia in NO release in-vivo.nIt is emerging that the effects of insulin on endothelial function are complex and in part dependent on thenphysiological/pathophysiological environment present when insulin binds to its receptor on the endothelial cell surface.nThe present article reviews the evidence for insulin being a pro-atherosclerotic and anti-atherosclerotic peptide withnparticular reference to endothelial cell derived NO bioavailability. In the present review we attempt to clarify the complexnrelationship between insulin, endothelial function and the risk of atherosclerosis by using data from in-vivo and ex-vivonmodels.